Medicine and Health Sciences Commons^™

Rapamycin Rescues Vascular, Metabolic And Learning Deficits In Apolipoprotein E4 Transgenic Mice With Pre-Symptomatic Alzheimer’S Disease, Ai-Ling Lin, Jordan B. Jahrling, Wei Zhang, Nicholas Derosa, Vikas Bakshi, Peter Romero, Veronica Galvan, Arlan Richardson

Sanders-Brown Center on Aging Faculty Publications

Apolipoprotein E ɛ4 allele is a common susceptibility gene for late-onset Alzheimer's disease. Brain vascular and metabolic deficits can occur in cognitively normal apolipoprotein E ɛ4 carriers decades before the onset of Alzheimer's disease. The goal of this study was to determine whether early intervention using rapamycin could restore neurovascular and neurometabolic functions, and thus impede pathological progression of Alzheimer's disease-like symptoms in pre-symptomatic Apolipoprotein E ɛ4 transgenic mice. Using in vivo, multimodal neuroimaging, we found that apolipoprotein E ɛ4 mice treated with rapamycin had restored cerebral blood flow, blood–brain barrier integrity and glucose metabolism, compared …

Antioncogenic And Oncogenic Properties Of Nrf2 In Arsenic-Induced Carcinogenesis, Young-Ok Son, Poyil Pratheeshkumar, Ram Vinod Roy, Andrew Hitron, Lei Wang, Sasidharan Padmaja Divya, Mei Xu, Jia Luo, Gang Chen, Zhuo Zhang, Xianglin Shi

Center for Research on Environmental Disease Faculty Publications

Arsenic (As³⁺) is a carcinogen with considerable environmental and occupational relevancy. The present study shows that As³⁺-transformed human lung bronchial epithelial BEAS-2B cells (AsT cells) exhibit the property of apoptosis resistance. The level of basal reactive oxygen species (ROS) is very low in AsT cells in correlation with elevated expressions of both antioxidant enzymes and antiapoptotic proteins. Nuclear factor erythroid 2-related factor (Nrf2) and p62 are constitutively expressed. These two proteins up-regulate antioxidant enzymes and antiapoptotic proteins. The knockdown of Nrf2 or p62 by small interfering RNA (siRNA) enhanced both ROS levels and As³⁺-induced …

Tuberculosis And Cardiovascular Disease: Linking The Epidemics, Moises A. Huaman, David Henson, Eduardo Ticona, Timothy R. Sterling, Beth A. Garvy

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The burden of tuberculosis and cardiovascular disease (CVD) is enormous worldwide. CVD rates are rapidly increasing in low- and middle-income countries. Public health programs have been challenged with the overlapping tuberculosis and CVD epidemics. Monocyte/macrophages, lymphocytes and cytokines involved in cellular mediated immune responses against Mycobacterium tuberculosis are also main drivers of atherogenesis, suggesting a potential pathogenic role of tuberculosis in CVD via mechanisms that have been described for other pathogens that establish chronic infection and latency. Studies have shown a pro-atherogenic effect of antibody-mediated responses against mycobacterial heat shock protein-65 through cross reaction with self-antigens in human vessels. Furthermore, …

Commentary On "Systemic Candidiasis And Cytomegalovirus Infection In The Setting Of Artificial Cardiac Device Deployment", Moises A. Huaman

The VAD Journal

No abstract provided.

Chronic Ldh Elevation After Left Ventricular Assist Device Implantation, Hesham R. Omar, Navin Rajagopalan, Maya Guglin

The VAD Journal

A 61-year-old woman who underwent HeartMate II left ventricular assist device placement for non-ischemic cardiomyopathy developed elevated lactate dehydrogenase within two weeks after implantation. After eight months of observation and several hospital admissions during which there was no evidence of pump thrombosis, she presented with clinically manifest hemolysis. During pump exchange there was notable pannus formation on the inflow cannula of the left ventricular assist device. The pannus around the inflow likely existed for several months, limiting the flow and creating a low-grade hemolysis and this low flow state stimulated thrombus formation triggering gross hemolysis. Thoratec analysis of the pump …

Preliminary Evaluation Of The Disease Surveillance System During Influenza Outbreaks Of Pandemic Scale, Eric Meisheri, Diana M. Prieto, Peter Holvenstot, Richard Vanenk

Frontiers in Public Health Services and Systems Research

In the United States it is currently unknown whether the influenza surveillance system is capable of producing timely and accurate data for case estimation during an outbreak of pandemic scale. This simulation provides a preliminary evaluation of the surveillance system’s ability to collect data and produce timely and accurate trends of cases confirmed with an influenza virus. For the evaluation, a computer-based simulation of the data-collection process was used, which was validated with real demographic and epidemiologic information. The results were analyzed to determine the most significant behavioral and operational factors influencing the data collection and to propose the exploration …

Plasminogen Activator Inhibitor-1 In Cigarette Smoke Exposure And Influenza A Virus Infection-Induced Lung Injury, Yashodhar P. Bhandary, Shwetha K. Shetty, Amarnath S. Marudamuthu, Krishna K. Midde, Hong-Long Ji, Homoyoun Shams, Renuka Subramaniam, Jian Fu, Steven Idell, Sreerama Shetty

Center for Research on Environmental Disease Faculty Publications

Parenchymal lung inflammation and airway and alveolar epithelial cell apoptosis are associated with cigarette smoke exposure (CSE), which contributes to chronic obstructive pulmonary disease (COPD). Epidemiological studies indicate that people exposed to chronic cigarette smoke with or without COPD are more susceptible to influenza A virus (IAV) infection. We found increased p53, PAI-1 and apoptosis in AECs, with accumulation of macrophages and neutrophils in the lungs of patients with COPD. In Wild-type (WT) mice with passive CSE (PCSE), p53 and PAI-1 expression and apoptosis were increased in AECs as was lung inflammation, while those lacking p53 or PAI-1 resisted AEC …

Old Dog, New Tricks - Usefulness Of The Ecg In Monitoring Acute Rejection Post Cardiac Transplantation, Paul Anaya, Samy-Claude Elayi

The VAD Journal

Electrocardiographic abnormalities have been described in the setting of acute rejection following orthotopic cardiac transplantation. The following is a brief commentary related to an interesting case report by Goldraich et al. which was recently published in the VAD Journal.

The Role Of Apob-Containing Lipoproteins In Abdominal Aortic Aneurysm, Jing Liu

Theses and Dissertations--Pharmacology and Nutritional Sciences

Abdominal aortic aneurysm (AAA) is a devastating disease that exhibits permanent lumen expansion typically in the infrarenal aorta. AAA is prevalent among aged population, especially in males. Despite the incidence in women is lower, studies indicate the tortuosity is more severe and aortic rupture risk is higher in women. In most patients, AAA remains asymptomatic until it ruptures leading to sudden and fatal hemorrhage.

To date, there is no proven medical therapy that can prevent the expansion or rupture. Human observational studies implicate the presence of AAA is associated with both high plasma low-density lipoprotein-cholesterol (HDL-C) and low plasma high-density …

Syphilis: The Forgotten Sexually Transmitted Disease. A Brief Case Report, Amy Burnett, Hatim A. Omar

Pediatrics Faculty Publications

Syphilis has declined significantly over the last 30 years. Due to that success, many physicians no longer have the skills to recognize its symptoms. We present a case of syphilis as a demonstration of this fact.

Emotional Enhancement And Repetition Effects During Working Memory In Persons With Mild Cognitive Impairment, Lucas S. Broster

Theses and Dissertations--Clinical and Translational Science

This dissertation introduces a framework for understanding differences in how emotional enhancement effects might influence memory in aging adults and then summarizes the findings of three studies of how repetition effects and emotional enhancement effects influence working memory in older adults without cognitive impairment (NC), older adults with amnestic mild cognitive impairment (MCI), and older adults with mild Alzheimer’s disease (AD). In these experiments, individuals with AD showed cognitive impairment in terms of accuracy and reaction time, but individuals with MCI showed milder behavioral impairment that was confined to manipulations of working memory. Individuals with AD showed relative sparing of …

Chemoenzymatic Studies To Enhance The Chemical Space Of Natural Products, Jhong-Min Chen

Theses and Dissertations--Pharmacy

Natural products provide some of the most potent anticancer agents and offer a template for new drug design or improvement with the advantage of an enormous chemical space. The overall goal of this thesis research is to enhance the chemical space of two natural products in order to generate novel drugs with better in vivo bioactivities than the original natural products.

Polycarcin V (PV) is a gilvocarcin-type antitumor agent with similar structure and comparable bioactivity with the principle compound of this group, gilvocarcin V (GV). Modest modifications of the polyketide-derived tetracyclic core of GV had been accomplished, but the most …

Cardiovascular Disease Risk Factors In Structural Firefighters, Nicholas W. Trubee

Theses and Dissertations--Kinesiology and Health Promotion

This dissertation is composed of two manuscripts assessing cardiovascular disease (CVD) risk in structural firefighters. Study 1 compared traditional CVD risk factors and health-related behaviors between professional and volunteer firefighters. Online questionnaires were sent to approximately 4000 firefighters in the state of Kentucky. The results indicated that 90% of volunteer and 58% of professional firefighters were classified as moderate-to-high CVD risk. Volunteer firefighters were significantly (p < 0.001) older and more likely (p = 0.026) to be current cigarette smokers. The mean body mass index among all firefighters in the sample was 30.8 kg·m^-2. Nearly 60% of volunteer firefighters were obese. Obese firefighters were more likely (p < 0.05) to have been diagnosed as diabetic or pre-diabetes compared to overweight and normal weight firefighters. These results indicate that volunteer firefighters may be at a greater CVD risk compared to professional firefighters.

Study 2 investigated the association of cardiorespiratory fitness (CRF) and body fat with arterial stiffness in professional firefighters. Forty-six …

Impact Of Starch Source On Equine Hindgut Microbial Ecology, Brittany Elizabeth Davis Harlow

Theses and Dissertations--Animal and Food Sciences

Grain inclusion in equine diets can allow starch to reach the hindgut where bacteria compete for the substrate. The hypothesis was that starch introduction would cause a source-dependent press disturbance in equine fecal microflora. Fecal cell suspensions were prepared by differential centrifugation and re-suspension in media with ground corn, oats or wheat. At 24 h, corn had more amylolytics and Group D Gram-positive cocci (GPC), and fewer lactate-utilizing (LU) bacteria and lactobacilli than oats, with wheat being intermediate. Predominant amylolytics were identified by their 16S RNA gene sequence as Enterococcus faecalis (corn, wheat) and Streptococcus bovis (oats). In an in …

Examining The Relationship Between Type And Extent Of After-School Care Use And High Bmi In Children Ages 5-17, Morgan E.B. Chojnacki

DNP Projects

Objectives: The purpose of this study was to examine the relationship between body mass index (BMI) and after-school care use in school age children and adolescents in Kentucky. The specific aims of this study were to examine differences in BMI groups (high versus normal/low) by: a) type and b) extent of after-school care use.

Methods: Parents of children age 5-17 years were administered a 21-item survey which assessed the amount of time their children spent in specific types of after-school care. BMI of the child/adolescent participants were obtained at the time of the survey. High BMI was defined …

Dietary Selenium Supplementation: Effects On Neurodegeneration Following Traumatic Brain And Spinal Cord Injury, Carolyn A. Crowdus Meyer

Theses and Dissertations--Neuroscience

Traumatic brain and spinal cord injury continue to be substantial clinical problems with few available treatment strategies. Individuals who are at a greater risk for sustaining a central nervous system (CNS) injury, such as professional athletes and military personnel, may benefit from a prophylactic supplement that would intervene in the neurodegenerative pathways immediately following injury. The high demand for selenium within the central nervous system, as well as the synthesis of selenoproteins by neurons and astrocytes suggests a critical role of selenium within the brain and spinal cord. Studies were designed to test the efficacy of enriched dietary selenium status …

Comparing Must And The Nri Tools In The Identification Of Malnutrition In Heart Failure Patients, Cassondra D. Degener

DNP Projects

The purpose of this project was to test the performance of albumin, NRI and MUST screening tools in comparison to the standardized measure of prealbumin among HF patients admitted to the University of Kentucky Chandler Medical Center. Inclusion criteria included all HF patients with the 428 diagnostic code, admitted from January 1, - December 31, 2013, ages 18 and older, with all laboratory values available specified in the data collection tool (Appendix A). A retrospective electronic medical record (EMR) review was performed for 100 patients who met the inclusion criteria. All data were collected through the University of Kentucky’s secure …

Regulation Of Pancreatic Β-Cell Function By The Renin-Angiotensin System In Type 2 Diabetes, Robin C. Shoemaker

Theses and Dissertations--Pharmacology and Nutritional Sciences

Diet-induced obesity promotes type 2 diabetes (T2D). Drugs that inhibit the renin-angiotensin system (RAS) have been demonstrated in clinical trials to decrease the onset of T2D. Previously, we demonstrated that mice made obese from chronic consumption of a high-fat (HF) diet have marked elevations in systemic concentrations of angiotensin II (AngII). Pancreatic islets have been reported to possess components of the renin-angiotensin system (RAS), including angiotensin type 1a receptors (AT1aR), the primary receptor for AngII, and angiotensin converting-enzyme 2 (ACE2), which negatively regulates the RAS by catabolizing AngII to angiotensin-(1-7) (Ang-(1-7)). These two opposing proteins have been implicated in the …

Clinical And Pathologic Significance Of Integrin Α6Β4 Expression In Human Malignancies, Rachel L. Stewart

Theses and Dissertations--Clinical and Translational Science

Integrins are cellular adhesion molecules that bind cells to the extracellular matrix. The integrin α6β4, a receptor for laminins, is predominantly expressed on epithelial cells where it is present at the basal surface adjacent to the basement membrane. This integrin plays a critical role in maintaining normal cellular functions, yet has also been implicated in promoting invasion and metastasis in human malignancies. While overexpression of the integrin α6β4 has been detected in select human cancers, the clinical significance of integrin α6β4 expression in a number of malignancies has not been determined. The purpose of this study was to examine integrin …